Investigation of the Effect of Dimethyl Fumarate on T Cells in Patient

A 24-week, Multicenter, Exploratory, Two Arm Study to Assess the Effect of Dimethyl Fumarate on Immune-Modulatory Action on T Cells in Patients With Relapsing Remitting Multiple Sclerosis (DIMAT-MS)

CompletedPhase 4Relapsing MSNCT024610692014-003481-25

What it found

Paper found, not read

A paper reports the results; we have not read it yet. See Papers below.

What was tested

Treatment tested

What it measured

Main measures

  • Expression of lymphocyte phenotypic surface markers in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis.

    0, 8, 16 and 24 weeks after initiation of investigational treatment (week 0)

    Immune response

  • Expression of lymphocyte phenotypic surface markers in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis and untreated healthy subjects.

    0, 8, 16 and 24 weeks after initiation of investigational treatment (week 0)

    Immune response

  • changes in lymphocyte subpopulations upon dimethyl fumarate (Tecfidera)-treatment in RRMS patients at week 8, 16 and 24 compared to baseline.

    Immune response

Other measures (7)

  • T cell effector functions in terms of cytokine production of CD4+ and CD8+ in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis.

    0, 8, 16 and 24 weeks after initiation of investigational treatment (week 0)

    Immune response

  • T cell effector functions in terms of cytokine production of CD4+ and CD8+ in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis and untreated healthy subjects.

    0, 8, 16 and 24 weeks after initiation of investigational treatment (week 0)

    Immune response

  • Migratory capacity of immune cells (percentage of migrated cells) in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis.

    0 and 24 weeks after initiation of investigational treatment (week 0)

    Immune response

  • Migratory capacity of immune cells (percentage of migrated cells) in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis and untreated healthy subjects.

    0 and 24 weeks after initiation of investigational treatment (week 0)

    Immune response

  • Mitochondrial energy metabolism of T cells upon dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis.

    0 and 24 weeks after initiation of investigational treatment (week 0)

  • Mitochondrial energy metabolism of T cells upon dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis and untreated healthy subjects.

    0 and 24 weeks after initiation of investigational treatment (week 0)

  • changes in T cell effector functions, in terms of cytokine production of CD4+ and CD8+ T cells derived of PBMC of dimethyl fumarate (Tecfidera)-treated patients at weeks 8, 16 and 24 as compared to baseline.

    Immune response

Who could take part

Relapsing MS · 18 to 60 · EDSS 0 to 6.0

Show the full criteria

Inclusion criteria

Healthy subjects: * H-1. Written informed consent must be obtained before any assessment is performed. * H-2. Male and female subjects aged 18 - 60 years. * H-3. No history of multiple sclerosis or clinically isolated syndrome. * H-4. No history of other autoimmune diseases, which has been treated systemically with corticosteroids, immunomodulators or immunosuppressive drugs at any time point. RRMS patients: * MS-1. Written informed consent must be obtained before any assessment is performed. * MS-2. Male and female subjects aged 18 - 60 years. * MS-3. Patients with RRMS, defined by 2010 revised McDonald criteria. * MS-4. Patients with an Expanded Disability Status Scale (EDSS) score of 0-6.0. * MS-5. Patients with one of the following treatment status: * Naïve to disease modifying (DM) treatment (i.e. no DM treatment for at least 1 month), * Currently on MS therapy with interferon β-1 or glatiramer acetate and willing to switch to dimethyl fumarate (Tecfidera®). * MS-6. MRI-scan of the brain ≤ 3 months at screening.

Exclusion criteria

RRMS patients: * MS-1. Known hypersensitivity to dimethyl fumarate or any ingredients of Tecfidera® (microcrystalline cellulose; croscarmellose-sodium; talcum; high dispersion, hydrophobic silicon dioxide; magnesiumstearate (Ph. Eur.); triethylcitrate; methacrylic acid-methacrylate copolymer (1:1) (Ph. Eur.); methacrylic acid-ethylacrylate copolymer (1:1)-dispersion 30% (Ph. Eur.), simeticon, sodiumdodecylsulfate, polysorbate 80, gelantine, titanium oxide (E171), brilliant blue (E133), hydrated Iron(III)-oxide hydroxide (E172), shellac, potassium hydroxide. * MS-2. A MS-relapse within 30 days prior to screening. * MS-3. Known history of active tuberculosis or active tuberculosis determined by a positive QuantiFERON® TB Gold test (i.e. a negative test result has to be provided at screening unless a negative test result exists from the last 3 months prior to screening). * MS-4. Moderate to severe impairment of liver function or persisting elevations > 2 x ULN (confirmed by retest) of serum glutamic pyruvic transaminase/ alanine aminotransferase (SGPT/ALT) or serum glutamic oxaloacetic transaminase/aspartate aminotransferase (SGOT/AST), except patients with confirmed Gilbert´s syndrome (Meulengracht´s disease). * MS-5. Moderate to severe impairment of renal function, as shown by serum creatinine > 133 μmol/L (or > 1.5 mg/dL). * MS-6. Patients with significantly impaired bone marrow function or significant anemia, leukopenia, neutropenia or thrombocytopenia. * MS-7. Women of childbearing potential not utilizing highly effective contraception. Both populations: * MS/H-1. Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study. * MS/H-2. Subjects unlikely to comply with protocol as determined by investigator, e.g., uncooperative attitude, inability to return for follow-up visits (e.g. major physical disability), and known unlikelihood of completing the study. * MS/H-3. Clinically relevant cardiovascular, neurological, endocrine, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult or that would put the subject at risk by participating in the study. * MS/H-4. Subjects with ulcerative colitis or Crohn´s disease. * MS/H-5. Subjects with a congenital or acquired severe immunodeficiency, a history of cancer (except for basal or squamous cell skin lesions which have been surgically excised, with no evidence of metastasis), lymph proliferative disease, or any subject who has received lymphoid irradiation. * MS/H-6. Human immunodeficiency virus (HIV) positive, hepatitis B virus positive or hepatitis C virus positive subjects (i.e. a negative test result has to be provided at screening. In the presence of a negative test result from the last 3 months prior to screening, the test has not to be repeated at screening.). * MS/H-7. Acute or chronic infection. * MS/H-8. History of drug or alcohol abuse. * MS/H-9. Use of adrenocorticotrophic hormone (ACTH) or systemic corticosteroids for 4 weeks prior to screening. * MS/H-10. Prior or concomitant use of cytokine therapy or intravenous immunoglobulins in the 3 months prior to screening. * MS/H-11. Prior use of alemtuzumab or cladribine. * MS/H-12. Prior use (within 1 year) of fingolimod (Gilenya®) or natalizumab (Tysabri®). * MS/H-13. Prior use (within 2 years) of mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporine, methotrexate or mycophenolate mofetil. * MS/H-14. Prior treatment with teriflunomide or leflunomide, unless successful wash-out, confirmed by plasma concentration of \< 0.02 μg/ml. * MS/H-15. Prior use of any investigational drug in the 6 months preceding screening. * MS/H-16. Pregnant or breast-feeding women.

As registered. Criteria can change, so ask the trial team or your neurologist.

About this trial

In the sponsor's words

This is an exploratory study, which allows analysis of multiple immune parameters derived from peripheral blood mononuclear cells (PBMCs) from patients with relapsing remitting multiple sclerosis before and during immune-modulatory treatment with dimethyl fumarate in comparison to PBMCs from healthy subjects.

Papers

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History

    1. Started

      May 2015

    2. Main results due

      Jan 2018

    3. Finished

      May 2018

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